P505 - PERILIPIN 5 DEFICIENCY ALLEVIATES METABOLIC ASSOCIATED FATTY LIVER DISEASE BY INHIBITING FERROPTOSIS

P505

PERILIPIN 5 DEFICIENCY ALLEVIATES METABOLIC ASSOCIATED FATTY LIVER DISEASE BY INHIBITING FERROPTOSIS

Y. Tang^1,*, P. Zheng¹, Y. Li², X. Wang¹, W. Yan³, X. Yin¹, Y. Xia¹, X. Zhu¹, W. Cui¹, L. Dong¹, Y. Wang¹, L. Liu¹, T. Guo¹, D. Yu¹, K. Li¹

¹Henan Key Laboratory of Rehabilitation Medicine, Henan Joint International Research Laboratory of Chronic Liver Injury and Henan Provincial Outstanding Overseas Scientists Chronic Liver Injury Workshop,, the Fifth Affiliated Hospital of Zhengzhou University, ²Henan Key Laboratory of Rehabilitation Medicine, Henan Joint International Research Laboratory of Chronic Liver Injury and Henan Provincial Outstanding Overseas Scientists Chronic Liver Injury Workshop,, the Fifth Affliated Hospital of Zhengzhou University, ³ Rehabilitation Medicine, Zhengzhou Health College, Zhengzhou, China

Rationale: Metabolic associated fatty liver disease (MAFLD) has been widely recognized as the most common chronic liver disease globally. Our previous work suggested that perilipin (PLIN5) deficiency attenuated HFD-induced MAFLD in mice model. However, the underlying mechanism remains unclear. In this report, we explore the link of PLIN5 to ferroptosis and elucidate its effect on MAFLD.

Methods: PAOA-treated AML12 cells and HFD-induced mice model were hired for experiments in the study.  Firstly, we confirmed the link of PLIN5 to ferroptosis in MAFLD. Next, we investigated how PLIN5 contributed to ferroptosis in vivo and in vitro experiments. Furthermore, we explored the role of TF3/CHOP/CHAC1 axis in PLIN5-induced ferroptosis in progression of MAFLD.

Results: Our data showed that knockout of PLIN5 ameliorated MAFLD and inhibited ferroptosis, while overexpression of PLIN5 aggravated ferroptosis and oxidative damage, indicating that PLIN5 impacted on the progression of MAFLD by affecting ferroptosis. Analysis using the ferroptosis database combined with transcriptomics revealed that PLIN5 affected the expression of ATF3. CHOP and CHAC1 were down-regulated in the PLIN5^-/- HFD group compared with the WT HFD group. Moreover, the expression of ATF3/CHOP/CHAC1 induced by PLIN5 overexpression was reversed by FER-1. ATF3 knockdown alleviated lipid accumulation and ferroptosis induced by PLIN5 overexpression. 

Conclusion: PLIN5 delete may alleviate MAFLD by inhibiting ferroptosis, which provide novel insights for understanding the progression of MAFLD.

Disclosure of Interest: None declared